Single photon emission computed tomography (SPECT) of regional cerebral blood flow (RCBF) has been employed experimentally in the assessment of patients with dementia. The standard with which the SPECT diagnosis has been compared previously has been the initial clinical diagnosis. Recognizing that histopathologic diagnosis would be a more reliable standard, the authors compared SPECT diagnoses and clinical diagnoses with histopathologic diagnoses in a series of 18 patients who had been referred by the Alzheimer Disease Research Center. SPECT RCBF studies were carried out prospectively in 15 patients with an inhaled xenon-133 SPECT technique and in three patients with technetium-99m hexamethyl-propylene-amine oxime and triple-camera-scanner SPECT. When compared with histopathologic diagnosis, clinical diagnosis was correct in 15 of 18 patients; visual scanning diagnosis, in 13 of 18; and Xe-133-SPECT diagnosis based on quantitative ratios in regions of interest, in 14 of 15 (13 of 13 with Alzheimer disease).